N-acetylcysteine loaded electrospun core/shell nanofibers: a promising system for ferroptosis in spinal cord injury

Spinal cord injury (SCI) induces a cascade of secondary damage mechanisms, including oxidative stress, inflammation, and cell death, which severely impair neuronal recovery. In this study, N-acetylcysteine (NAC), a thiol-based antioxidant with limited CNS bioavailability, was encapsulated in polycaprolactone (PCL) nanofibers using emulsion electrospinning. This approach allows localized and sustained drug delivery. Span 80 and Poloxamer 407 were used as surfactants to stabilize the emulsion and increase the hydrophilicity of the fibers. The resulting core/shell nanofibers (NAC-CSN) exhibited uniform morphology, improved wettability, and favorable mechanical properties, while supporting cell viability and migration in vitro. Sustained NAC release over several days was achieved, indicating diffusion-controlled delivery. In a rat model of SCI, NAC-CSN treatment attenuated oxidative and ferroptotic damage and promoted early neuroregeneration, which enabled measurable locomotor recovery. These findings suggest that NAC-CSN scaffolds offer an effective neuroprotective strategy against secondary SCI damage and, by enabling localized antioxidant delivery at the lesion site, represent a clinically applicable platform for future tissue engineering and translational therapies.